Genotype-phenotype analysis of ocular findings in Rubinstein-Taybi syndrome – A case report and review of literature

ABSTRACT

Background

Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome with a wide range of phenotypic presentations, including characteristic facial features. A variety of ocular abnormalities have been described in patients with RSTS. The genetic etiology of RSTS is heterogeneous but often involves two major genes, CREBBP (cAMP-response element binding protein-binding protein) and EP300 (E1A binding protein p300), with CREBBP variants responsible for the majority of the cases.

Materials and Methods

We report a new case of female patient with a novel variant in CREBBP (c.4495C>G), with clinical features consistent with RSTS. We performed a literature review to search for possible genotype-phenotype relationships between the type of variant in CREBBP and frequency of ocular presentations. A PubMed search generated 12 articles that met our inclusion criteria. With the addition of our patient, there were a total of 163 patients included for mutation analysis (164 variants given one patient had two different variants).

Results

Our review revealed that the most common variant types were frameshift (25%), gross deletion (23%), nonsense (18%), and intragenic deletions (13%). There does not appear to be an obvious hot spot location. A total of 127 patients were included for genotype-phenotype analysis of ocular features (36 patients were excluded as unable to discern variant type). The most frequent ocular features in patients with RSTS were down-slanting palpebral fissure (74%), arched eyebrows (56%), long eyelashes (52%), and strabismus (23%).

Conclusions

Our results suggest that currently there is no clear genotype-phenotype relationship between the type of variant and frequency of associated ocular features in RSTS patients.

KEYWORDS:

• Rubinstein-Taybi syndrome
• CREBBP
• EP300
• holoprosencephaly
• broad thumbs
• strabismus
• glaucoma

Disclosure statement

Natario L. Couser, MD, MS:

1)Retrophin, Inc./Travere Therapeutics, Inc. (Clinical Trial)

2)National Cancer Institute/Children’s Oncology Group (Clinical Trial)

3)Elsevier (Book editor)

4)Patient-Centered Outcomes Research Institute (PCORI; Advisory Panel on Rare Disease)

5)National Institutes of Health/National Eye Institute (Grant Review Panelist)

The other authors declared they have no conflicts of interest.

Consent

Written consent has been obtained.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.